Differential immune regulation of mir-155 in tumor growth (P2113)

Abstract

Abstract MiR-155 is upregulated in both myeloid and lymphoid cells following their activation. To address the role of host miR-155 in tumor growth, we examined the contribution of miR-155 to antitumor immunity using multiple models of syngeneic solid tumor growth in mice. Host miR-155 deficiency inhibited growth of transplanted LLC1 lung tumor cells but not B16 melanoma cells. Interestingly, there was a specific contribution of both T-cell-intrinsic and dendritic cell-intrinsic function of miR-155 positively regulating antitumor T cell immunity. However, host miR-155 deficiency did not lead to overt immune suppression, and instead stimulated robust T-cell- mediated antitumor immunity. On the other hand, the accumulation and function of myeloid-derived suppression cells (MDSC) were impaired in tumor- bearing mice lacking miR-155 and miR155-deficient MDSCs failed to induce T cell antigen unresponsiveness. Moreover, in vivo tumor-inhibitory effect of MDSC depletion by 5-FU was completely abrogated in miR155-deficient mice. Thus, the net antitumor effects of host miR-155 deficiency indicate that the impairment of immunosuppressive MDSCs possibly outweighs the potential suppressive effects of miR-155 deficiency in T cell and dendritic cell compartments. Our study identifies the differential immune regulation for miR-155 during tumor growth, and provides valuable insights for therapeutically intervention in cancer or autoimmune diseases using highly specific methods of modulating miRNAs.